Proteomics, the study of proteins and their functions, is currently a focus of both university and commercial investment as each discovery in proteomics holds the potential to unlock yet another advance in medical science. The extreme variability in the chemistry of proteins in biological systems and especially in mammals, presents special problems.
A recurring problem with respect to proteomics involves the poor solubility of a large percentage of proteins such as those found in lipid membranes and other hydrophobic areas of the cell or in the cellular environment. This is because many of the systems developed for the study of proteins are geared to analysis in an aqueous environment. To isolate hydrophobic proteins or hydrophobic protein domains, surfactants (detergents, such as sodium dodecyl sulfate (SDS) or triton X) are commonly employed. Surfactants generally have a polar head group and a hydrophobic tail group and encapsulate hydrophobic proteins wherein the hydrophobic tail is in contact with the hydrophobic protein and the polar groups are in contact with the water. Thus, hydrophobic proteins and polypeptides are sequestered in a coating of detergent wherein the complex is soluble in an aqueous environment.
However, many analytical systems are sensitive to the presence of surfactants. For example, SDS and triton X suppress the analyte signal during matrix assisted laser desorption ionization mass spectrometry (MALDI MS) analysis. Signal suppression from surfactant contamination is contemplated to result from physical and chemical blockage of the ionization/desorption process of MALDI MS.
What is needed are surfactant compositions and methods suitable for MALDI-MS analyses, and other analyses, of hydrophobic molecules including natural and synthetic polymers and polypeptides/proteins.
International Publication WO 00/70334 to Lee et al., discloses certain surfactants and results for electrospray mass spectroscopy (MS) analysis of myoglobin in the presence of certain of the surfactants.
U.S. Pat. No. 4,713,486 to Buckle discloses certain arachidonic acid analogues, including certain cinnamates, stated to be useful in the treatment of allergic diseases.
U.S. Pat. No. 5,114,851 to Porter et al., discloses certain light activated acyl-enzymes.
U.S. Pat. No. 5,218,137 to Porter et al., discloses certain compounds useful as an intermediate for making light-activatable acyl-enzymes.
Also see U.S. Pat. No. 5,808,300 to Caprioli, incorporated herein by reference, for a discussion of MALDI MS.
Additional background information may be found in the following publications: Kyte et al., J. Mol. Biol. (1982) 157(1):105-32; March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 5th Ed. by Michael B. Smith and Jerry March, John Wiley & Sons, Publishers; Wuts et al. (1999) Protective Groups in Organic Synthesis, 3rd Ed., John Wiley & Sons, Publishers; Behforouz, M.; Kerwood, J. E. Alkyl and Aryl Sulfenimides. J. Org. Chem., 34 (1), 51-55 (1969); and Harpp, D. N.; Ash, D. K.; Back, T. G.; Gleason, J. G.; Orwig, B. A.; VanHorn, W. F. A New Synthesis of Unsymmetrical Disulifdes. Tetrahedron Letters, 41, 3551-3554 (1970).